Purpose. Substantial reductions in inpatient episodes of severe hypoglycemia achieved by a large healthcare system through enhanced use of technology and sustained quality-improvement initiatives are described. Summary: After internal data collection and analysis revealed that severe hypoglycemia accounted for 75% of all systematically monitored adverse drug events in its hospital network, St. Louis-based BJC HealthCare designed and executed a multifaceted approach to reducing hypoglycemia events. Initiated by a pharmacist-led task force, the project entailed (1) automated event detection and creation of dashboards for comparing hypoglycemia rates among at-risk patients at 11 BJC facilities, (2) implementation of evidence-based and internal best practices in use at BJC's top-performing hospitals, (3) development of an online "Hypoglycemic Event Analysis Tool" (HEAT) to support event investigation and collection of data on causative factors, and (4) the assembly of targeted interventions at a "Hypoglycemia Facility Strategy Tracking" (H-FaST) intranet site. As a result of the launch of the HEAT and H-FaST tools and associated provider education activities, the systemwide rate of hypoglycemia events in the specified at-risk patient population declined from 6.45 per 1000 patient-days during a preimplementation baseline period (July-December 2009) to 1.32 per 1000 patient-days during a designated postimplementation period (January-June 2014), an 80% overall reduction in hypoglycemia (p < 0.01); reductions in severe hypoglycemia events ranging from 70% to 100% were observed at all 11 hospitals. Conclusion: A multifaceted, evidence-based, data-driven approach enabled a large healthcare system to markedly reduce the frequency of severe hypoglycemia events.